One of the principal goals of modern organic chemistry is the development of new synthetic routes toward the controlled, efficient production of asymmetric compounds. Saturated carbon atoms, which constitute the backbone of most organic compounds, are attached to adjacent atoms through a tetrahedral arrangement of chemical bonds. If the four bonds are to different atoms or groups, the central carbon provides a chiral, or asymmetric center, and the compound therefore may have the ability to exist in two mirror-image, or enantiomeric forms. When synthetic organic chemists attempt preparation of these asymmetric compounds it is crucial to have a means to produce the desired enantiomer because compounds of the wrong enantiomeric form often lack the desired biological, physical or chemical properties. The present invention thus focuses on enantioselective acid catalysts, which are shown to provide a means toward the synthesis of compounds in a desired enantiomeric form.
The literature contains a number of reports of research on chiral Lewis acids and the results are summarized in a recent review paper [Narasaka, K., Synthesis, 1991, 1]. Transition metal catalysts designed for this purpose in general contain bidentate diol ligands as the source of chirality. This reflects the "fundamental concept" that such "C.sub.2 symmetry" ligands will provide especially high enantioselectivity [Whitesell, J. K., Chem. Rev. 1989, 89, 1581]. Accordingly, there have been no reported attempts to use optically active trialkanolamines, which lack C.sub.2 symmetry, as chiral ligands in asymmetric Lewis acids.
Previous research on early transition metal trialkanolamine complexes focused on compounds containing a chiral triethanolamine. For example, complexes have been described containing derivatives of titanium [Bostwick, C. O., U.S. Pat. No. 2,824, 114 (1958); Chem. Abstr. 1958, 52, 7743], zirconium [Taube, R.; Knoth, P. Z., Anorg. Allg. Chem. 1990, 581, 89], vanadium [Astakhov, A. I.; Kas'yanenko, A. I., Izv. Vyssh. Ucheb. Zaved., Khim. Khim. Tekhnol. 1972, 15, 1620 (Chem Abstracts, 1973, Vol. 78 no. 66407)], niobium [Mehrota, R. C.; Kapoor, P. N., J. Indian Chem. Soc. 1867, 44, 467], and tantalum [Mehrota, R. C.,; Kapoor, P. N., Indian J. Chem. 1967, 5, 505]. There is an extensive literature on catalytic uses of triethanolamine titanate, for example, for cross-linking epoxy resins [Bokalo, G. A.; Omel'chenko, S. I.; Zapunnaya, K. V., Vysokomol. Soedin., Ser. B. 1979, 21, 371. Chem. Abstr. 1979, 91, 40289], and at least one catalytic application of a triethanolamine vanadate [Kane, B. J., U.S. Pat. No. 4,254,291 (1981). Chem. Abstr. 1981, 94, 47554].
Also known in the art are examples of chiral but racemic trialkanolamine complexes. These include a vanadium complex of triisopropanolamine [Tandura, S. N.; Voronkov, M. G.; Kisin, A. V.; Shestakov, E. E.; Ovchinnikova, Z. A.; Baryshok, V. P., Zh. Obsch. Chem. 1984, 54, 2012 (English Trans. p 1795)] as well as titanium analogues [Voronkov, M. G.; Faitel'son, F. D., Khim. Geterosikl. Soedin. 1967, 39. Chem. Abstr. 1967, 67, 64321].
One reported complex of an early transition metal with an optically active trialkanolamine involves a ligand wherein the asymmetry resides in only one "arm" of the trialkanolamine, and the asymmetric carbon is bound to nitrogen [Liu, H.; Yin, C. Gaodeng Xuexiao Huaxue Xuedbao 1989, 10, 1257. Chem. Abstr. 1989, 113, 125232].
Other related art includes two reports of borate esters of enantiomerically pure triisopropanolamine [Morrison, J. D.; Grandbois, E. R.; Weisman, G. R. in "Asymmetric Reactions and Processes in Chemistry" (A.C.S. Symposium Series, No. 185) American Chemical Society, Washington, D.C., 1982; Grassi, M.; DiSilvestro, G.; Farina, M. Tetrahedron 1985, 41, 177]. The first of these papers describes the use of the corresponding borohydride as a stoichiometric chiral reducing agent.
Early transition metal complexes containing the achiral dialkanolamine diethanolamine are likewise known [Mehrota, R. C.; Kapoor, P. N.; J. Indian Chem. Soc. 1967, 44, 467; Indian J. Chem. 1967, 5, 505].
The asymmetric addition of azidotrimethylsilane is the subject of two reports. In the first, titanium isopropoxide was treated with various chiral diols or aminoalcohols in an effort to obtain a homogeneous catalyst [Emziane, M.; Sutowardoyo, K. I.; Sinou, D., J. Organometal. Chem. 1988, 346, C7]. The catalytic addition proceeded but the product was essentially racemic. A modest enantiomeric excess ["ee"] was obtained by running the reaction stoichiometrically. The other report uses transition metal tartrates as heterogeneous catalysts [Yamashita, Y., Bull. Chem. Soc. Japan 1988, 61, 1213]. Using zinc tartrate, a 42% ee was claimed for a 14 day reaction.
There are also many reports of catalytic addition of trimethylsilyl cyanide to epoxides [Matsubara ,S.; Onishi, H.; Utimoto, K., Tetrahedron Lett. 1990, 31, 6209] but not reports of asymmetric additions. On the other hand, the asymmetric addition of trimethylsilyl cyanide to aldehydes has been reported by three research groups [Reetz, M. T.; Kyung, S.-H.; Bolm, C.; Zierke, T., Chem. Ind. (London), 1986, 824; Narasaka, K.; Yamada, T.; Minamikawa, H., Chem. Lett. 1987, 2073; Hyashi, M.; Matsuda, T.; Oguni, N., J. Chem. Soc., Chem. Commun. 1990, 1364]. All three examples involve the use of titanium alkoxides as homogeneous asymmetric catalysts.
A significant body of research on the asymmetric catalysts of the addition of organometallic reagents such as diethylzinc to carbonyl compounds exists and this research has been summarized in a recent review [Noyori, R.; Kitamura, M., Angew. Chem., Int. Ed. Engl. 1991, 30, 49]. These procedures typically involve adding an optically active aminoalcohol to a mixture of diethylzinc and the carbonyl compound with no early transition metal being present. In one case an optically active dialkanolamine has been used for this purpose, against in the absence of an early transition metal [Chaloner, P. A.; Langadianou, E., Tetr. Lett. 1990, 36, 5185]. On the other hand, optically active titanium complexes have been used to catalyze the asymmetric addition of diethylzinc to aldehydes [Yoshioka, M.; Kawakit, T.; Ohno, M., Tetr. Lett. 1989, 30, 1657; Schmidt, B.; Seebach, D., Angew. Chem., Int. Ed. Engl. 1991, 30, 99]. In these cases the ligands are diols or diamides of C.sub.2 symmetry. In one case, a methyltitanium complex coordinated to an N-sulfonated derivative of an aminoalcohol has been used for the stoichiometric alkylation of aldehydes [Reetz, M. T.; Kuekenhoener, T.; Weinig, P., Tetr. Lett. 1986, 27, 5711].
Thus, although significant advances have been made in the field of asymmetric catalysis, a clear need exists for the development of new procedures for the controlled organic synthesis of asymmetric compounds. It is the object of this invention to provide a new class of chiral Lewis acid catalysts which will be useful in the preparation of asymmetric products.